scholarly journals The Pseudo-Symmetric N-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation

2021 ◽  
Author(s):  
Rosarita D'Orsi ◽  
Maria Funicello ◽  
Paolo Lupattelli ◽  
Federico Berti ◽  
Lucia Chiummiento
Keyword(s):  
Biological Evaluation ◽  
Inhibition Activity ◽  
Diversity Oriented Synthesis ◽  
Docking Analysis ◽  
The Core ◽  
In Vitro Inhibition ◽  
High Yields ◽  
Heterocyclic Moiety ◽  
Hiv 1

New series of compounds containing both heterocycle moieties and pseudo-symmetric hydroxyethylamine core were obtained using a simple synthetic path that can provide a library of compounds in few steps and high yields. Furthermore, diversity-oriented synthesis was studied to change different functionalities according to needs. The in vitro inhibition activity against recombinant HIV-1 protease was evaluated. A beneficial effect of this class of compounds can be obtained either for the presence of a bis-benzyl group into the core and for the heterocyclic moiety in P1, specifically the indole ring. Docking analysis was also reported.

scholarly journals Synthesis of 3,15-Disuccinate-12-Coumarin Substituted Andrographolide Derivatives and Their Antiplatelet Aggregation Activities In Vitro

2020 ◽  
Vol 15 (5) ◽  
pp. 1934578X2091086
Author(s):  
Xue Li ◽  
Jiang-Wei Wang ◽  
Bin Huang ◽  
Zhi-Xiang Peng ◽  
Yuan-Yuan Zhang ◽  
...  
Keyword(s):  
Adenosine Diphosphate ◽  
Biological Evaluation ◽  
Significant Inhibition ◽  
Inhibition Activity ◽  
Antiplatelet Aggregation ◽  
Candidate Structure ◽  
Dependent Behavior ◽  
Aggregation Activity ◽  
Dose Dependent

In order to develop a series of novel compounds with antiplatelet aggregation activities, 3,15-disuccinate-12-coumarin substituted derivatives were designed and synthesized based on the natural product andrographolide. In vitro antiplatelet aggregation activities were evaluated by the turbidimetric method with thrombin, adenosine diphosphate (ADP), arachidonic acid (AA), and collagen as inducers. The biological evaluation revealed that compound 11k showed significant inhibition activity for thrombin, AA, and collagen-induced platelet aggregation at the same time and exhibited a dose-dependent behavior. Compound 11c showed the highest antiplatelet aggregation activity induced by ADP. Most of the derivatives had no significant cytotoxicity. Therefore, our work proved that 3,15-disuccinate-12-coumarin substituted andrographolide derivatives had the potential to become a novel candidate structure for antiplatelet aggregation and deserved further study.

scholarly journals F18, a Novel Small-Molecule Nonnucleoside Reverse Transcriptase Inhibitor, Inhibits HIV-1 Replication Using Distinct Binding Motifs as Demonstrated by Resistance Selection and Docking Analysis

2011 ◽  
Vol 56 (1) ◽  
pp. 341-351 ◽  
Author(s):  
Xiaofan Lu ◽  
Li Liu ◽  
Xu Zhang ◽  
Terrence Chi Kong Lau ◽  
Stephen Kwok Wing Tsui ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Small Molecule ◽  
Mononuclear Cells ◽  
Binding Motif ◽  
Drug Resistant ◽  
Peripheral Blood Mononuclear ◽  
Docking Analysis ◽  
Hiv 1 ◽  
Calanolide A

ABSTRACTNonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication. We previously described a newly synthesized small molecule, 10-chloromethyl-11-demethyl-12-oxo-calanolide A (F18), a (+)-calanolide A analog, as a novel anti-HIV-1 NNRTI (H. Xue et al., J. Med. Chem. 53:1397–1401, 2010). Here, we further investigated its antiviral range, drug resistance profile, and underlying mechanism of action. F18 consistently displayed potent activity against primary HIV-1 isolates, including various subtypes of group M, circulating recombinant form (CRF) 01_AE, and laboratory-adapted drug-resistant viruses. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM), which was in stark contrast to the extensively used NNRTIs nevirapine and efavirenz. Moreover, we induced F18-resistant viruses byin vitroserial passages and found that the mutation L100I appeared to be the dominant contributor to F18 resistance, further suggesting a binding motif different from that of nevirapine and efavirenz. F18 was nonantagonistic when used in combination with other antiretrovirals against both wild-type and drug-resistant viruses in infected peripheral blood mononuclear cells. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore,in silicodocking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase differently from other NNRTIs. This study presents F18 as a new potential drug for clinical use and also presents a new mechanism-based design for future NNRTI.

scholarly journals In vitro inhibition of HIV-1 replication in autologous CD4+ T cells indicates viral containment by multifactorial mechanisms

2017 ◽  
Vol 32 (6) ◽  
pp. 485-494
Author(s):  
Ting Tu ◽  
Jianbo Zhan ◽  
Danlei Mou ◽  
Wei Li ◽  
Bin Su ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
In Vitro Inhibition ◽  
Hiv 1

scholarly journals Organoselenium mild electrophiles in the inhibition of Mpro and SARSCoV-2 replication

2020 ◽  
Author(s):  
Luca Sancineto ◽  
Francesca Mangiavacchi ◽  
Agnieszka Dąbrowska ◽  
Agata Pacuła ◽  
Magdalena Obieziurska-Fabisiak ◽  
...  
Keyword(s):  
Cytopathic Effect ◽  
Selenium Atom ◽  
Inhibition Activity ◽  
Exchange Processes ◽  
Main Protease ◽  
In Vitro Inhibition ◽  
Complex Scenario ◽  
Detoxification Process

New Ebselen-like derivatives resulted to be very strong in vitro inhibitors of SARS-CoV-2 main protease. We demonstrated that this activity mainly depends on the electrophilicity of the selenium atom that is considerably higher in the N-substituted 1,2- benzoselenazol-3(2H)-ones respect to the corresponding diselenides allowing it to be rapidly attached by free thiols affording sulfur-selenium intermediates that are further subjected to thiol exchange processes. This data paints a very complex scenario that requires us to consider Ebselen and Ebselen-like derivatives as potential electrophilic substrates for the several other free thiols present in the cell beside the target free cysteine. The sulfur selenium intermediates are milder electrophiles that could be theoretically implicated in both the detoxification process as well as in the final enzymatic inhibition. We here demonstrated that the in vitro inhibition activity is not fully reproduced in the prevention of viral replication in the cell-based assay. This indicates that the structure of the substituents introduced in the Ebselen scaffold is a crucial factor to control the reactivity of the selenated molecule in the network of thiol exchanges, as well as for molecular recognition of the targeted enzymatic cysteine. For this reason, an in-depth investigation is strongly desirable to better understand how to increase the activity and the selectivity of Ebselen derivatives overcoming the issues of the apparent PAINS-like role of Ebselen. Furthermore, besides the antiviral activity, thee selected compounds also showed a different ability to reduce the virus-induced cytopathic effect, indicating that other mechanisms could be implicated. One may consider here the well-known cytoprotective antioxidant activity of Ebselen and its derivatives.<p></p>

Clastogenic Factors In Plasma Of HIV-1 Infected Patients Activate HIV-1 Replication In Vitro: Inhibition By Superoxide Dismutase

1997 ◽  
Vol 23 (4) ◽  
pp. 571-578 ◽  
Author(s):  
Marvin A. Edeas ◽  
Ingrid Emerit ◽  
Yacine Khalfoun ◽  
Yamina Lazizi ◽  
Lidia Cernjavski ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
In Vitro Inhibition ◽  
Hiv 1

Enhanced In Vitro Inhibition of HIV-1 Replication by 3′-Fluoro-3′-deoxythymidine Compared to Several Other Nucleoside Analogs

1988 ◽  
Vol 4 (6) ◽  
pp. 457-466 ◽  
Author(s):  
HEINZ HARTMANN ◽  
MARKUS W. VOGT ◽  
AMY G. DURNO ◽  
MARTIN S. HIRSCH ◽  
GERHARD HUNSMANN ◽  
...  
Keyword(s):  
Nucleoside Analogs ◽  
In Vitro Inhibition ◽  
Hiv 1

Phenanthridine derivatives as promising new anticancer agents: synthesis, biological evaluation and binding studies

2020 ◽  
Vol 12 (8) ◽  
pp. 709-739 ◽  
Author(s):  
Iqbal Azad ◽  
Rumana Ahmad ◽  
Tahmeena Khan ◽  
Mohammad Saquib ◽  
Firoj Hassan ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Dna Cleavage ◽  
High Resolution Mass Spectrometry ◽  
Biological Evaluation ◽  
Binding Studies ◽  
Binding Properties ◽  
One Pot ◽  
Docking Analysis ◽  
Dna Cleavage Activity

Aim: Phenanthridines are an essential class of nitrogenous heterocycles with extensive applications in medicinal chemistry. The development of efficient and eco-friendly methods for the preparation of chirally pure dihydropyrrolo[1,2- f]phenanthridines (5a–h), and their in vitro evaluation and modeling studies as potential anticancer, antioxidant and DNA cleavage agents is reported. Methodology & results: Compounds 5a–h were prepared through a facile one-pot synthesis and characterized by infrared, high resolution mass spectrometry, 1H and 13C nuclear magnetic resonance. The molecules were subjected to virtual screening and docking analysis against selected human molecular targets. Compound 5g displayed good binding properties as well as significant anticancer and DNA cleavage activity. Conclusion: Compound 5g has been identified as a potential lead candidate for further testing against additional cancer cell lines and animal models in future.

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